Numerous studies have shown that there are endocrine abnormalities associated with endogenous depression. The major alterations include resistance of the serum cortisol rhythm to suppression by dexamethasone (dex), alterations in the circadian secretion pattern of serum cortisol, and a blunted thyrotropin stimulating hormone (TSH) response to thyrotropin releasing hormone (TRH). However, the exact relationship between these endocrine alterations and the depression remains unknown. It is possible that these endocrine abnormalities may be associated with certain non-specific features of depression rather than with the depression per se. For example, depressed subjects have altered sleep patterns including decreased slow-wave sleep (SWS), fragmentation of sleep, and early morning awakening. Because sleep is one of the basic synchronizers of not only the normal rest-activity cycle in humans but also of many endocrine and metabolic events, and since hormone secretion is altered during sleep in patients with affective disorders, we hypothesize that some hormonal alterations observed in depressed patients may be mediated primarily by the sleep disturbance. In fact, the endocrine responses to dex and TRH in depressed patients may be normal responses which are desynchronized with respect to time, as a consequence of the disturbances in sleep. We intend to examine these chronoendocrine variables in normal volunteers and endogenously depressed patients before and after sleep deprivation. The number of subjects or patients chosen for each of the experiments outlined in this proposal will be determined by statistical power analysis of already published or pilot data to minimize the chance of a type II (beta) statistical error.